Primary neuroendocrine carcinoma of the mediastinum. (33/327)

A mediastinal mass was found in a 37 year old male who presented with fever, weight loss and fatigue. The chest CT revealed a 9x6x4 cm well circumscribed mass located paratrachaelly in the upper mid-mediastinum. The mass was removed by right thoracotomy. Macroscopically the tumor weighed 195 g and measured 9x6x4 cm. Microscopically the tumor consisted of small blue cells in solid and trabecular pattern. Immunohistochemical studies performed for differential diagnosis of small blue cell tumors. The tumor was diagnosed as primary neuroendocrine carcinoma of the mediastinum. This case is presented for its rare recurrence in that particular location.  (+info)

Calcification in large cell neuroendocrine carcinoma of the lung. (34/327)

BACKGROUND: The aim was to investigate the prevalence of intratumoral calcification in large cell neuroendocrine carcinoma (LCNEC) and to review computed tomography (CT) and histological findings. PATIENTS AND METHODS: From August 1992 through March 2000, 35 out of 1183 surgically resected lung cancer patients were histologically diagnosed as having LCNEC at our institute. We reviewed the plain radiographs and CT scans of these 35 LCNEC patients. In LCNEC cases with intratumoral calcification, we examined the size, number, distribution and pattern of intratumoral calcifications visible on the CT scans and the histological features. RESULTS: Three cases (9%) exhibited calcification. The calcifications were recognized by CT scans alone. The CT scans showed punctate or eccentric intratumoral calcifications, which are considered to be a malignant feature, in all three cases. In two cases, the calcifications were histologically confirmed to be located within the necrotic areas of a tumor nest. CONCLUSION: We found three LCNEC cases with intratumoral calcification. The prevalence of LCNEC calcification was similar to that in previous reports on lung cancer. The mechanism of the intratumoral calcification in our LCNEC cases is speculated to be dystrophic calcification.  (+info)

Prognostic implications of neuroendocrine differentiation and hormone production in patients with Stage I nonsmall cell lung carcinoma. (35/327)

BACKGROUND: Approximately 10-20% of nonsmall cell lung carcinomas (NSCLC) show neuroendocrine (NE) differentiation, as evaluated by panendocrine markers or ultrastructural evidence of dense-core secretory granules. However, little is known regarding the prevalence and clinical implications of NE differentiation in patients with Stage I NSCLC. METHODS: The authors analyzed 220 consecutive patients with Stage I NSCLC (pT1-T2N0M0) among 2100 patients with primary lung carcinoma who underwent surgical treatment between 1987 and 1993. Using light microscopy and immunohistochemical staining for synaptophysin, chromogranin A, and respiratory tract-related hormones, 28 NSCLC specimens with NE differentiation (NSCLC-ND) and 11 large cell neuroendocrine carcinoma (LCNEC) specimens were identified. RESULTS: The 28 NSCLC-ND specimens included 15 adenocarcinomas and 13 squamous cell carcinomas. Neoplastic cells with NE features never exceeded 20% in NSCLC-ND specimens, whereas neoplastic cells amounted to 20-90% in LCNEC specimens. NSCLC-ND specimens with > 5% NE-differentiated tumor cells showed increased Ki-67 labeling index (P = 0.007) and invasive phenotype, as evaluated by fascin immunoreactivity (P = 0.021). Patients with adenocarcinoma, but not with squamous cell carcinoma, who had > 5% NE-differentiated cells had a worse clinical course compared with patients who had ordinary NSCLC, with reduced overall survival (P = 0.017) and disease free survival (P = 0.049). In multivariate analysis, NE differentiation > 5% neoplastic cells in patients with adenocarcinoma independently predicted a poorer prognosis (hazard ratio, 2.61; 95% confidence interval, 0.99-6.85). Hormone production was restricted to chromogranin positive NSCLC-ND but did not affect prognosis. CONCLUSIONS: Stage I adenocarcinomas with >or= 5% NE tumor cells are clinically aggressive tumors, similar to LCNEC. Hormone production identifies a more fully developed neuroendocrine phenotype but is not relevant to prognosis. The identification of NE-differentiated cells in patients with NSCLC may have clinical relevance.  (+info)

Classification of multiple cancer types by multicategory support vector machines using gene expression data. (36/327)

MOTIVATION: High-density DNA microarray measures the activities of several thousand genes simultaneously and the gene expression profiles have been used for the cancer classification recently. This new approach promises to give better therapeutic measurements to cancer patients by diagnosing cancer types with improved accuracy. The Support Vector Machine (SVM) is one of the classification methods successfully applied to the cancer diagnosis problems. However, its optimal extension to more than two classes was not obvious, which might impose limitations in its application to multiple tumor types. We briefly introduce the Multicategory SVM, which is a recently proposed extension of the binary SVM, and apply it to multiclass cancer diagnosis problems. RESULTS: Its applicability is demonstrated on the leukemia data (Golub et al., 1999) and the small round blue cell tumors of childhood data (Khan et al., 2001). Comparable classification accuracy shown in the applications and its flexibility render the MSVM a viable alternative to other classification methods. SUPPLEMENTARY INFORMATION: http://www.stat.ohio-state.edu/~yklee/msvm.htm  (+info)

Somatostatin receptor scintigraphy versus chromogranin A assay in the management of patients with neuroendocrine tumors of different types: clinical role. (37/327)

BACKGROUND: Current diagnosis and staging of neuroendocrine tumors (NETs) are significantly improved by the introduction of the chromogranin A (CgA) assay in plasma or serum as a tumor marker, and by the use of somatostatin receptor scintigraphy (SRS) for tumor localization. However, the clinical role of CgA assay compared with SRS in the management of NETs has not been well elucidated. PATIENTS AND METHODS: Sixty-three consecutive patients with a histological diagnosis of NET underwent plasma CgA assay and SRS for tumor staging (23 cases), evaluation of tumor response (18 cases) and evaluation of tumor recurrence on follow-up (22 cases). Twenty-one patients had well-differentiated neuroendocrine tumors (WDNETs: 18 gastroenteropancreatic tumors and three lung NETs); 22 patients had well-differentiated neuroendocrine carcinomas (WDNECs: 17 gastroenteropancreatic carcinomas, two lung neuroendocrine carcinomas and three neuroendocrine carcinomas of unknown origin) and 20 patients had poorly differentiated neuroendocrine carcinomas (PDNECs: 14 extra-pulmonary small-cell carcinomas and six Merkel cell carcinomas). Almost all (58 of 63) NETs were non-functioning. The quantitative determination of CgA was performed in plasma using an enzyme immunoassay with a cut-off value fixed at 34 U/l. Scintigraphies with indium 111-DTPA-octreotide ((111)In-pentetreotide) included whole-body images and single photon emission computed tomography (SPECT) scans of the chest and abdomen. RESULTS: SRS results were compared with CgA findings and final clinical data. The overall sensitivity of SRS and CgA, based on the final clinical data, was 77% and 55%, respectively, whereas the specificity of both SRS and CgA was 94%. Concerning tumor type, SRS accuracy was 95% for WDNETs, 86% for WDNECs and 60% for PDNECs; CgA accuracy was 76% for WDNETs, 68% for WDNECs and 50% for PDNECs. With regard to disease extent, SRS sensitivity was 100% for limited disease and 72% for advanced disease; CgA sensitivity was 43% for limited disease and 57% for advanced disease. CONCLUSIONS: In our NET series, SRS proved to be more sensitive than CgA, with equivalent specificity. Tumor differentiation influences the sensitivity of SRS and CgA analysis. In addition, the plasma CgA level is related to tumor secretory activity. Nevertheless both SRS and CgA should be considered useful tools in the diagnostic work-up of NET patients.  (+info)

Diagnostic findings of bronchial brush cytology for pulmonary large cell neuroendocrine carcinomas: comparison with poorly differentiated adenocarcinomas, squamous cell carcinomas, and small cell carcinomas. (38/327)

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the lung has been proposed as a new disease entity. To establish diagnostic features, bronchial brush cytologic findings were evaluated. METHODS: Bronchial brush cytology material of 20 LCNECs was evaluated by light microscopy and stained immunocytochemically with protein gene product 9.5 (PGP9.5), neuron-specific enolase, and neural cell adhesion molecule antibodies. The findings were compared with those for 19 poorly differentiated adenocarcinomas (ACs), 18 poorly differentiated squamous cell carcinomas (SCCs), and 20 small cell lung carcinomas (SCLCs). RESULTS: Frequently observed characteristic cytologic findings of LCNECs were necrotic background (90.0%), large tumor cell size (90.0%), naked nuclei (90.0%), and nuclear streaking (90.0%). Nuclei in all LCNECs showed a fine granular chromatin pattern and possessed one or a few nucleoli. Indian-filing and rosette arrangements were observed in less than one-half of the LCNECs. In poorly differentiated ACs and SCCs, these features were less frequent, whereas thick nuclear membranes were observed more often. In SCLCs, tumor cell adhesions and Indian-filing or nuclear molding were observed more frequently than in LCNECs, whereas a necrotic background, tumor cell clusters, large tumor cells, and nucleoli were less prominent. The majority of LCNECs (80.0%) had a positive immunocytochemical reaction for PGP9.5, in contrast to the low positive reactions for ACs (42.1%) and SCCs (30.8%). CONCLUSIONS: Large cell neuroendocrine carcinomas can be diagnosed preoperatively by bronchial brush cytology using reliable parameters, including tumor cell size, naked nuclei, thin nuclear membranes, nuclear streaking, high PGP9.5 positivity, and a necrotic background.  (+info)

Immunohistochemical staining of cytologic smears with MIB-1 helps distinguish low-grade from high-grade neuroendocrine neoplasms. (39/327)

Neuroendocrine neoplasms (NENs) of the lung and gastrointestinal tract constitute a pathologic and biologic spectrum of tumors. Accurate cytologic diagnosis of a neuroendocrine neoplasm is important since definitive treatment frequently is based on low- and high-grade categories without histologic sampling. In many instances, however, low- and high-grade NENs share cytologic features, hindering a precise classification. Since the histologic diagnostic criteria for separation of low- from high-grade categories can be based on the proliferation rate, we proposed to evaluate the usefulness of the immunocytochemical stain for the proliferation marker MIB-1 in the grading of NENs. Cytologic preparations of 63 NENs were retrieved from the files of Memorial Sloan-Kettering Cancer Center, New York, NY. One representative alcohol-fixed slide from each case was destained and restained immunocytochemically for MIB-1. When MIB-1 immunoreactivity was considered, all low-grade NENs showed immunoreactivity in fewer than 25% of the neoplastic cells, and all high-grade NENs demonstrated immunoreactivity in more than 50% of neoplastic cells. Our study demonstrates that MIB-1 dramatically stratifies NENs as low-grade or high-grade. Therefore, the proliferation index also correlates with grade of NEN in cytology specimens.  (+info)

Distinct patterns of chronic gastritis associated with carcinoid and cancer and their role in tumorigenesis. (40/327)

A series of 60 gastric endocrine tumors comprised 44 body-fundus argyrophil carcinoids, of which 23 arose in a background of hypergastrinemia and type A chronic atrophic gastritis (A-CAG), mainly with histologic patterns suggestive of an autoimmune process. Only 22 percent (compared with 19 percent of 58 tumor-free A-CAG cases) of 36 carcinoids and 21 percent of 19 A-CAG carcinoids investigated had Helicobacter pylori (HP) colonization, against 50 percent of 14 CAG-associated neuroendocrine carcinomas or mixed endocrine-exocrine tumors, 84 percent of 150 cases with early gastric cancer (p < 0.001 versus carcinoids), mostly with B- or AB-type CAG, 76 percent of 97 tumor-free AB-CAG, and 95 percent of 151 tumor-free B-CAG cases. Secondary hypergastrinemia and local mechanisms activated by chronic autoimmune gastritis are among factors involved in the pathogenesis of relatively indolent CAG-associated carcinoids, whereas active HP gastritis in cooperation with environmental carcinogens may likely cause more severe epithelial transformation, leading to ordinary cancer and, possibly, to neuroendocrine carcinomas or mixed endocrine-exocrine tumors.  (+info)